alpha/beta tcd hct in patients with inherited bmf disorders

Conditions: Fanconi Anemia; Severe Aplastic Anemia; Myelodysplastic Syndromes; T Cell Receptor Alpha/Beta Depletion; Telomere Biology Disorder; Bone Marrow Failure; Dyskeratosis Congenita

Summary: this is a phase ii trial of t cell receptor alpha/beta depletion (α/β tcd) peripheral blood stem cell (pbsc) transplantation in patients with inherited bone marrow failure (bmf) disorders to eliminate the need for routine graft-versus-host disease (gvhd) immune suppression leading to earlier immune recovery and potentially a reduction in the risk of severe infections after transplantation.


Eligibility criteria:
patient selection: inclusion criteria: for fa patients: * diagnosis of fanconi anemia * age \<65 years of age * has one of the following risk factors: * severe aplastic anemia (saa) * myelodysplastic syndrome (mds) * high risk genotype * immunodeficiency associated with history of recurrent infections * karnofsky performance status ≥ 70% if ≥ 16 years of age or lansky play score ≥ 50% for patients \<16 years of age * adequate pulmonary, cardiac and liver function * voluntary written consent (minor assent if appropriate) prior to the performance of any study related procedures not part of standard medical care for tbd patients: • diagnosis of tbd * age \<70 years of age * has one of the following risk factors: * severe aplastic anemia (saa) * myelodysplastic syndrome (mds) * karnofsky performance status ≥ 70% if ≥ 16 years of age or lansky play score ≥ 50% for patients \<16 years of age * adequate pulmonary, cardiac and liver function * voluntary written consent (minor assent if appropriate) prior to the performance of any study related procedures not part of standard medical care exclusion criteria: * pregnant or breastfeeding as the treatment used in this study are pregnancy category d. females of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days of study registration * active, uncontrolled infection within 1 week prior to starting study therapy * malignant solid tumor cancer within previous 2 years donor selection (inclusion criteria): meets one of the following match criteria: * an hla-a, b, drb1 matched sibling donor (matched sibling) * an hla-a, b, drb1 matched related donor (other than sibling) * a related donor mismatched at 1 hla-a, b, c and drb1 antigen * 7-8/8 hla-a,b,c,drb1 allele matched unrelated donor per current institutional guidelines patients and donors are typed for hla-a and b using serological or molecular techniques and for drb1 using high resolution molecular typing. if a donor has been selected on the basis of hla-a, b, c and drb1 typing as above, preference will be made for donors matched at the hla-c locus. * body weight of at least 40 kilograms and at least 12 years of age * willing and able to undergo mobilized peripheral blood apheresis * in general good health as determined by the medical provider * adequate organ function defined as: * hematologic: hemoglobin, wbc, platelet within 10% of upper and lower limit of normal range of test (gender based for hemoglobin) * hepatic: alt \< 2 x upper limit of normal * renal: serum creatinine \< 1.8 mg/dl * performance of a donor infectious disease screen panel including cmv antibody, hepatitis b surface antigen, hepatitis b core antibody, hepatitis c antibody, hiv 1/2 antibody, htlva 1/2 antibody, treponema, and trypanosoma cruzi (t. cruzi) plus hbv, hcv, wnv, hiv by nucleic acid testing (nat); and screening for evidence of and risks factors for infection with zika virus, or per current standard institutional donor screen - must be negative for hiv and active hepatitis b * not pregnant - females of childbearing potential must have a negative pregnancy test within 7 days of mobilization start * voluntary written consent (parent/guardian and minor assent, if \< 18 years) prior to the performance of any research related procedure